Sex-Specific Effects of Microglia-Like Cell Engraftment during Experimental Autoimmune Encephalomyelitis
| Autor: | Kai Zhou, Jinming Han, Harald Lund, Keying Zhu, Ramil Hakim, Sreenivasa Raghavan Sankavaram, Klas Blomgren, Robert A. Harris, Xing-Mei Zhang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Central Nervous System
Male medicine.medical_treatment experimental autoimmune encephalomyelitis microglia neuroinflammation lcsh:Chemistry Mice Medicine lcsh:QH301-705.5 Spectroscopy Mice Knockout Microglia biology Experimental autoimmune encephalomyelitis General Medicine Computer Science Applications Cytokine medicine.anatomical_structure Cytokines Female monocytes microglial repopulation Encephalomyelitis Autoimmune Experimental Multiple Sclerosis Central nervous system Article Catalysis Myelin oligodendrocyte glycoprotein Inorganic Chemistry Immune system Animals Physical and Theoretical Chemistry Molecular Biology Neuroinflammation business.industry Macrophages Multiple sclerosis Organic Chemistry Histocompatibility Antigens Class II Macrophage Activation medicine.disease Mice Inbred C57BL Disease Models Animal Tamoxifen lcsh:Biology (General) lcsh:QD1-999 Immunology biology.protein Myelin-Oligodendrocyte Glycoprotein business |
| Zdroj: | International Journal of Molecular Sciences Volume 21 Issue 18 International Journal of Molecular Sciences, Vol 21, Iss 6824, p 6824 (2020) |
| ISSN: | 1422-0067 |
| Popis: | BackgroundMultiple Sclerosis (MS) is a chronic neuroinflammatory disorder of the central nervous system (CNS) that usually presents in young adults and predominantly in females. Microglia, a major resident immune cell in the CNS, are critical players in both CNS homeostasis and disease. We have previously demonstrated that microglia can be efficiently depleted by the administration of tamoxifen in Cx3cr1CreER/+Rosa26DTA/+ mice, with ensuing repopulation deriving from both the proliferation of residual CNS resident microglia and the engraftment of peripheral monocyte-derived microglia-like cells. MethodsTamoxifen was administered to Cx3cr1CreER/+Rosa26DTA/+ and Cx3cr1CreER/+ female and male mice. Experimental autoimmune encephalomyelitis (EAE), a widely used animal model of MS, was induced by active immunization with myelin oligodendrocyte glycoprotein one month after tamoxifen injections in Cx3cr1CreER/+Rosa26DTA/+ mice and Cx3cr1CreER/+ mice, a time point when the CNS niche was colonized by microglia derived from both CNS microglia and peripherally-derived macrophages. CNS myeloid cell compositions during acute and chronic EAE were measured by flow cytometry.ResultsWe demonstrate that engraftment of microglia-like cells following microglial depletion exacerbated EAE in Cx3cr1CreER/+Rosa26DTA/+ female mice as assessed by clinical symptoms and the expression of CNS inflammatory factors, but these findings were not evident in male mice. Higher major histocompatibility complex class II expression and cytokine production in the female CNS contributed to the sex-dependent EAE severity in mice following engraftment of microglia-like cells. ConclusionThe engraftment of microglia-like cells following microglial depletion exacerbated EAE in females. An underestimated yet marked sex-dependent microglial activation pattern may exist in the injured CNS during EAE. |
| Databáze: | OpenAIRE |
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